Altered B cell activation contributes to the immunopathogenesis of childhood arthritis-associated uveitis
- Bethany R. Jebson
- Benjamin Ingledow
- Vicky Alexiou
- Jakub Kubiak
- Persephone Jenkins
- Yuxuan Meng
- Melissa Kartawinata
- Restuadi Restuadi
- Wei-Yu Lin
- Chris Wallace
- Colin J. Chu
- Ameenat Lola Solebo
- Lucy R. Wedderburn
- Elizabeth C. Rosser
- Zoe Wanstall
- Fatjon Dekaj
- Aline Kimonyo
- Eileen Hahn
- Genevieve Gottschalk
- Freya Luling Feilding
- Alyssia McNeece
- Fatema Merali
- Elizabeth Ralph
- Emily Robinson
- Emma Sumner
- Andrew Dick
- Michael W. Beresford
- Emil Carlsson
- Joanna Fairlie
- Jenna F. Gritzfeld
- Oliver McClurg
- Karen Rafferty
- Athimalaipet V. Ramanan
- Teresa Duerr
- Michael Barnes
- Sandra Ng
- Kimme Hyrich
- Stephen Eyre
- Soumya Raychaudhuri
- Wendy Thomson
- John Bowes
- Jeronee Jennycloss
- Saskia Lawson-Tovey
- Paul Martin
- Andrew Morris
- Stephanie Shoop-Worrall
- Samantha Smith
- Michael Stadler
- Damian Tarasek
- Melissa Tordoff
2026-02-03
In Juvenile Idiopathic Arthritis (JIA), the most common childhood rheumatic disease, many patients also develop uveitis (JIA-uveitis), risking life-long vision loss. The mechanisms driving uveitis development in JIA remain understudied. Here, we demonstrate that peripheral blood CD19 + IgD - CD27 - double negative type 1 (DN1) B cells are elevated in JIA-uveitis compared to JIA patients without eye disease (JIA). The B cell receptor (BCR) repertoire was also more clonal and somatically hypermutated in JIA-uveitis and antigen-activated B cells infiltrated chronically inflamed JIA-uveitis eyes. Features of heightened B cell activation were recapitulated in experimental autoimmune uveoretinitis (EAU) and disrupting B and T cell interactions using monoclonal antibodies and transgenic mice suppresses uveitis. Together, these findings support a conceptual shift that uveitis is a primarily T cell driven disease and provide evidence for potential new therapeutic strategies that also consider B cells as drivers in disease pathology.